Implants comprising soft tissues may be implanted into a recipient to replace and/or repair existing soft tissues. For example, hereditary defects, disease, and/or trauma may damage soft tissues such that replacement and/or repair is desirable. These implants may be allografts, autografts, or xenografts, and the recipients may be human, mammal, or animal recipients. Implants are frequently used where the recipient is a human patient. Implants comprising soft tissues have been used, including in human patients, to replace heart valves, ligaments, tendons and skin, among other tissues.
It is desirable to treat implants, particularly autografts, allografts, and xenografts, to remove one or more undesirable components or to instill one or more desirable components. For example, implants may be passivated, or treated to remove or inactivate bacteria, viruses, fungi and other pathogens and antigenic constituents.
It is also well known to treat implants including implants comprising soft tissues with cleaning agents and/or gamma radiation. However, existing techniques suffer from one or more disadvantages. Undesirable results from radiation can include formation of radicals, hydrogen, and low-molecular-weight hydrocarbons; increased unsaturation; discoloration; and oxidation. The use of some chemical sterilizing agents (for example, glutaraldehyde) increases the risk that a toxic response will be evoked. Furthermore, some chemical sterilizing agents (for example, peroxides) may damage the implant, particularly soft tissues, which tend to be somewhat more fragile than bone and hard tissues. A particular concern with the passivation of implants comprising soft tissues is that treated soft tissue may suffer from increased laxity, reduced stiffness, reduced strength, or reduced biocompatibility, which can lead to variable performance of the implant. It is desirable to have treatment processes, including a process for passivation, that does not cause excessive laxity or reduction in stiffness or strength or biocompatibility of the soft tissue.
There is a continuing need in the art for a method of passivating implants comprising soft tissues that minimizes the possibility of immune rejection or infection. Further, there is a need in the art for a method of passivating implants comprising soft tissues which does not excessively damage the soft tissues. There is also a need for a method of passivating soft tissues that is quick, efficient, and results in a soft tissue with acceptable performance characteristics. U.S. Pat. No. 6,024,735 (“the '735 patent”) (LifeNet)—“Process and composition for cleaning soft tissue grafts optionally attached to bone and soft tissue and bone grafts produced thereby,” is directed to a method and composition for cleaning cadaveric soft tissue optionally attached to bone to produce soft tissue grafts optionally attached to bone suitable for transplantation into a human. The method involves removing bone marrow elements, blood deposits and any bacteria, virus or fungi contamination, from the donor bone and/or associated soft tissues. The '735 patent discloses a process in which bone graft and associated soft tissue is contacted with a first solvent that may include an alcohol, and a second solvent that may include hydrogen peroxide or an alcohol (col 14, line 65 to col. 16, line 34, and col. 17, line 53 to col. 18, line 56). Optional components (including hydrogen peroxide) may be added to either the first, second, third, or any subsequent solvents. (Id.) However, this process does not address damage from peroxide nor does it teach any method of protecting the tissues from such damage. Furthermore, the '735 patent states: “The order of use of solvents and the particular compositions of a particular solvent used in the present process is not critical as long as the first solvent used is a solvent containing one or more detergents.” (col. 17, lines 13-16).
U.S. Pat. No. 5,797,871 (“the '871 patent”) (LifeNet)—“Ultrasonic Cleaning of Allograft Bone,” is directed to a method for cleaning cadaveric donor bone to produce bone grafts suitable for transplantation into a human, as well as the bone grafts produced thereby. The method involves removing bone marrow potentially containing bacteria, virus or fungi, from the donor bone by sonicating the bone in a solvent containing one or more detergents to produce bone grafts essentially free from bone marrow. The solvent may contain, but is not limited to, one or more of the following: sterile water; saline; a detergent; an alcohol, for example, ethanol and/or isopropanol, solvents, a combination of solutes desired to facilitate solubilization of bone marrow; chelating agent; virucidal agent; bactericidal agent; antimycotic agent; sodium hydroxide or similar strong base, organic and/or inorganic acid and hydrogen peroxide. The '871 patent also discloses the use of decontaminating agents including, but not limited to, one or more of an antibacterial agent; an antiviral agent; an antimycotic agent; an alcohol for example, methyl, ethyl, propyl, isopropyl, butyl, and/or t-butyl; trisodium phosphate; sodium hydroxide; hydrogen peroxide; and/or any detergent. The '871 patent states that soft tissue debridement is not an essential element of the bone cleaning technology, but the '871 patent does not state that its cleaning method is suitable for cleaning soft tissues, nor does it address the issue of sterilant damage to soft tissues, not does it discuss methods of protecting soft tissue from such damage.
U.S. Pat. No. 5,769,893 (“the '893 patent”) (Shah) (which is a continuation-in-part application of U.S. Pat. No. 5,556,428) discloses an apparatus and method for inducing growth of soft tissues including skin, ligaments, tendons, blood vessels, and spinal cord which includes a tensioned spring causing the application of force on the soft tissue in the direction of the desired growth. The device also includes means for attaching the tensioned spring to the tissue and means for maintaining tension on the spring as the tissue grows. Further, a monitoring and control device can be included which can monitor and control the amount of growth.
U.S. Pat. No. 5,397,357 (“the '357 patent”) (Arthrex)—“Method For Preparing A Bone-Tendon-Bone Core Graft”, discloses a method for preparing a bone-tendon-bone core graft. A bone core is harvested from a patient and divided into two separate bone core halves. The bone core halves are inserted onto holding pins which are movably spaced along a work station. A harvested tendon is secured with suture onto the bone core halves, with the tendon extending therebetween to form the bone-tendon-bone core graft. The holding pins are supported by blocks which are moved apart along the work station to tension the bone-tendon-bone graft.
U.S. Pat. No. 5,333,626 (“the '626 patent”) (Cryolife)—“Preparation of Bone for Transplantation”, relates to a method of preparing bone for transplantation by maintaining the internal matrix of the bone to be implanted, preferably at high pressure, in the presence of a decontaminating agent, preferably polyvinyl pyrrolidine-iodine (PVP-I) optionally in the presence of a detergent, in solution. The '626 patent discloses a variety of other decontaminating agents which have been found to inactivate a wide range of infectious agents including bacteria, fungi, parasites and virus: hydrogen peroxide, ethanol, ozone, ethylene oxide, irradiation and mixtures thereof and with PVP-I. Although the '626 patent discloses that its procedure may be applied to bone blocks with attached connective tissue, it states that the connective tissue should not be subjected to the cleaning procedures: “If bone blocks with attached connective tissue are to be cleaned, the connective—tissue tendons, ligaments, menisci, for example—should be covered with a sterile covering such as plastic wrap or sterile drape during the cleaning procedure.” (col. 5, line 41-45).
U.S. Pat. No. 6,293,970 (“the '970 patent”) (Culp)—“Plasticized bone and soft tissue grafts and methods of making and using same,” is directed to a plasticized dehydrated or freeze-dried bone and/or soft tissue product. Water in the molecular structure of the bone or soft tissue matrix is replaced with one or more plasticizers. Permeation enhancers such as isopropanol may be used to facilitate permeation of plasticizer into bone or soft tissue. (col. 7, line 17).
Tissue sterilization methods known in the art have undesirable attributes. Gamma irradiation, in order to ensure destruction of pathogens, such as the human immunodeficiency virus (HIV), has been used at doses that result in tissue destruction (e.g. 3.5 Mrad; see, for example, Rasmussen, et al., J. Arthroscopic and Related Surgery, 10(2):188-197, (1994); Goertzen, et al., British Soc. of Bone and Joint Surg., 77:204-211 (805); Loty, et al., International Orthopaedics, 14:237-242, (1990)). Use of ethylene oxide has been found to result in implants that produce inflammatory responses (Kudryk, et al., J. Biomedical Materials, 26:1477-1488, (1992); Thoren, et al., Clin. Orthopaedics, 318:259-263, (1995); Simonian, et al., Clin. Orthopaedics, 302:290-296, (1994); Jackson, et al., Am. J. Sports Medicine, 18:1-9, (1990)). Standard chemical solution treatments, while effective in sterilizing surfaces with which the solutions are brought into contact, tend to be insufficiently penetrating to reach the interstices of tissues, where potentially pathogenic organisms may reside. With regard to sterilization of soft tissue, the potential for damage to the soft tissue by irradiation, ethylene oxide, or chemical solution treatment is of particular concern, because soft tissue are more susceptible to damage than bone tissue. Even milder sterilants such as peroxides may cause damage due to swelling of the tissues and the presence of residual reaction byproducts.
A desirable treatment process includes one or more of the following features: Effective removal or inactivation of a wide range of bacterial, viral and fungal pathogens; absence of graft toxicity; retention of desirable tissue characteristics, such as biomechanical strength or growth-inducing properties; effectiveness across a wide range of operating modifications and for a wide variety of tissue types; ability to conclude the process in a final implant tissue container, to ensure sterile packaging and delivery for implantation; ability to apply automated control and monitoring systems and develop an automated and validated process.